Figure: (a) Recombinant WT or P108S of SARS-CoV2 3CLpro were analysed with SDS-PAGE visualizing using CBB staining.
Figure: (b) The enzymatic activities of SARS-CoV2 3CLpro WT (circle) and P108S (square) were determined using a FRET-based substrate with the cleavage site of SARS CoV-2 3CLpro (Dabcyl-KTSAVLQ SGFRKME-Edans).
Figure: (c) The kinetic parameters of enzyme activity of 3CLpro WT and P108S were determined using GraphPad Prism 8 software by initial rate measurement of the substrate cleavage.
Figure: (d) Inhibitory activities of SARS-CoV2 3CLpro WT and P108S by GC376 were analyzed using a FRET-based cleavage assay.
Figure: Deuterium uptake curves for the peptides showing significant di
Figure: SARS-CoV-2 3CLpro P108S is declined its enzymatic activity by structural alteration.
Mutation Signatures and In Silico Docking of Novel SARS-CoV-2 Variants of Concern.
Result: The COH-VOC has two mutations at positions N501Y and D614G in the S-protein, while harboring several mutations in the NSP2 (T85I), NSP3 (T181I, A256V), NSP5 (L89F, P108S), NSP6 (G258E), NSP12 (P323L), NSP14 (N129D), and NSP16 (R216C), NS3 (Q57H, G172V), NS7a (
Microsecond molecular dynamics suggest that a non-synonymous mutation, frequently observed in patients with mild symptoms in Tokyo, alters dynamics of the SARS-CoV-2 main protease.
Discussion: Considering the differences in flexibility of the loop region at the entrance of the catalytic sites we observed between the WT and P108S mutant, the mechanism of drug binding might be different in the mutant from that of the WT main protease.
Discussion: Further, our finding that the catalytic dyad became less accessible upon the Discussion: It is also worth mentioning that our calculations dealt only with the P108S mutation, and we did not evaluate other mutations, which were predicted to be functionally neutral, found in patients in a previous study.
Discussion: Therefore, considering the prevalence of the mutation in patients, drug binding to the P108S mutant protease should be studied.
Discussion: Together with P108S, those mutations may also affect physicochemical properties of the main protease.
SARS-CoV-2 genetic variations associated with COVID-19 pathogenicity.
Impact of Early Pandemic Stage Mutations on Molecular Dynamics of SARS-CoV-2 M(pro).
PMID: 32853525
2020
Journal of chemical information and modeling
Result: Another cluster of mutations is distributed in domain II and includes 3 subgroups: a group of fully immobilized positions (A116V, A129V, P132L, T135I, and I136V), a group of bridging (hinge-like) sites that connect rigid and flexible regions (Y101C, R105H, P108S, N151D, V157I/L, C160S, A173V, and P184L/S), and a group of mostly mobile residues (T190I, A191V, and A193V
SARS_CoV_2 mutation literature information.
PMID: 
2022
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